There is recognition that a variety of methods can be used to detect hepatic disorders particularly in human patients. The methods are generally dominated by fluid-based tests that monitor liver-related molecules in blood, plasma and urine. See e.g., Handbook of Clinical Laboratory Data (1997) (CRC Press, Inc. West Palm Beach, Fla.)
However, many of the fluid-based tests for hepatic dysfunction are believed to be associated with significant drawbacks. For example, most of the tests are optimized to provide only an indirect measure of liver function. That is, the tests provide little or no information about how the liver functions in real-time. Significant patient follow-up and testing is often needed to achieve desired results. Additionally, there has been some concern that fluid-based tests may not always provide enough sensitivity or selectivity to detect mild hepatic disorders. Nearly all of the tests require handling of body fluids, thereby posing a biohazard risk to personnel conducting the tests.
Several attempts have been made to provide more effective methods for detecting hepatic disorders. For example, in one approach, a biopsy is taken from the patient to more precisely evaluate liver function. However, biopsy procedures are often costly, time-intensive and extremely painful. Biopsy procedures may also be unsuitable for patients suffering from specific hepatic disorders or patients who have received a liver transplant.
In another approach, it has been reported that it is possible to relate presence of certain volatile molecules in human breath to specific conditions. Several tests have been designed to detect these molecules. See e.g., Phillips, M., Sci. Am., (1992), 267: 74; Perman, J. A., Canad. J Physiol. Pharmac., (1991); 69: 111; Risby et al., Surgery, (1994), 115, 94; and Kazui et al., Free Radic Biol. Med., (1992), 13, 509; for disclosure relating to the prior breath tests.
More specific breath tests have been disclosed. For example, U.S. Pat. No. 5,386,832 discloses assays for measuring liver function by analyzing specific labeled molecules in human breath.
More particularly, it has been reported that specific sulfurous compounds such as volatile sulfides can be detected in the breath of some cirrhotic patients. It has been proposed that at least some of the compounds may arise from liver dysfunction. See e.g., Chen et al., J. Lab Clin. Med., (1970), 75: 628; Kaji et al., Clin. Chim. Acta, (1978), 85: 279; Tangernan et al., J. Lab Clin. Med., (1985), 106: 175 and Husamura, M., Nippon Naisa Gakkai Zasshi, (1979), 68: 1284.
However, the breath tests mentioned have been associated with problems which have tended to restrict use. For example, practically none of the tests are formatted to classify and/or stage a hepatic disorder. That is, the tests are not optimized to provide information as to what liver disorder is manifested by a patient and to what extent that disorder has progressed In addition, the tests usually cannot discriminate between different or closely related hepatic disorders. These shortcomings can negatively impact patient care in a variety of ways, e.g., by complicating diagnoses and/or delaying implementation of a life-saving therapy. The inability of the prior breath tests to stage hepatic disorders has made it especially difficult to evaluate patients in real-time.
Additionally, several of the prior breath tests have been reported to require administration of carbon 14 or other nuclides. Release of radioactive respiratory gas by patients may not be desirable for several reasons.
Many of the prior breath tests suffer from additional drawbacks and disadvantages. For example, as disclosed, the tests often require substantial breath samples, thereby restricting use to patients that can safely provide a substantial volume of breath. However, in many situations, patients may not be able to provide a large breath volume. Several specific breath tests require nearly all of the patient's breath sample, thereby eliminating opportunities to re-test the breath samples after analysis. In instances where more breath is needed, it can be very inconvenient or even impossible for patients to provide another breath sample. In cases where a patient's breath sample is exhausted, follow-up tests and statistical analyses can be difficult or impossible to perform, which compromises the accuracy of the analysis.
It has been disclosed that human breath includes perhaps hundreds of volatile organic molecules. However, only a fraction of these molecules are believed to relate to hepatic disorders. Accordingly, there is a need in the field to develop effective tests that can reliably characterize the disorders. In particular, it would be desirable to have test systems and methods that can facilitate reliable detection and preferably staging of hepatic disorders in a human patients.